Long-term maintenance of prognostic value of survivin and its relationship with p53 in T4 breast cancer patients

Abstract

Abstract. a large proportion of human tumors show deregulated expression of a variety of proteins that play a crucial role in the execution of the apoptotic program. Survivin belongs to the family of inhibitor of apoptosis proteins which were originally identified in baculoviruses. ectopic expression of survivin conveys resistance to apoptosis to a variety of stimuli, and survivin is one of the most abundantly overexpressed genes in human tumors such as breast cancer. in this study we examined the expression of survivin protein in a series of t4 breast cancers to identify any correlation with long-term patient outcomes. moreover, we investigated the hypothesis of a possible association between p53 and survivin as a factor further complicating the outcome. archival specimens from 53 t4 breast cancer patients were included in the study and treated for the immunohistochemical localization of survivin and p53 using the streptavidin-biotin alkaline phosphatase method. the immunoreactivity was evaluated semiquantitatively according to the percentage of cells stained. Forty percent of tumors were positive for survivin. Statistical analysis revealed that survivin expression negatively influenced the 5-and 10-year disease-free and overall patient survival. in multivariate analysis, survivin expression was a significant independent prognostic indicator of worse outcome in overall survival [hazard ratio (hr)=2.61]. Our results showed that survivin is associated with a worse prognosis in patients with t4 breast cancer, and remarkably its prognostic relevance is maintained even long-term. notably, p53 (hr=3.2) seems to negatively enhance the effect of survivin on survival. IntroductionBreast cancer is the most frequent tumor and the leading cause of cancer-related death among the female population worldwide (1). histopathological factors such as the size of the primary tumor, differentiation grade, the Ki-67 protein, the expression of estrogens (er) and progesterone (pgr) receptors or human epidermal growth factor receptor 2 (her2) and lymph node metastasis are associated with tumor prognosis (2). Identification of mechanisms underlying tumor cell invasion may contribute to develop new therapies that can arrest local invasion and metastatic spread of the disease.Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or Birc5, is a 16.5-kda protein which in humans is encoded by the BIRC5 gene (3,4). Survivin is a member of the inhibitor of apoptosis family that serves to inhibit caspase activation therefore leading to negative regulation of apoptosis or programmed cell death. Besides, it is known that survivin localizes to the mitotic spindle by interaction with tubulin during mitosis and may play an important role in regulating mitosis (5). Survivin is undetectable in terminally differentiated adult tissues, but becomes notably expressed in the most common human tumors, including stomach, colorectal, lung, breast, pancreatic and prostate cancers (6,7).Survivin expression can be deregulated in cancer by ...